Lisha Ma

The potential role of methyltransferase-like 5 in deficient mismatch repair of uterine corpus endometrial carcinoma

To explore the potential function of methyltransferase-like 5 (METTL5) in uterine corpus endometrial carcinoma (UCEC) and verify the relationship between deficient DNA mismatch repair (MMR) and METTL5. We used bioinformatics to predict the possible role of METTL5 and molecular biology methods to analyze METTL5 expression. We observed UCEC proliferation, development, and apoptosis using a METTL5 knockdown lentivirus and, coupled with METTL5 bioinformatics and Western blot analysis, detected microsatellite instability (MSI) and MMR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Finally, some METTL5-associated gene mutations in UCECs were detected. Results show that METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. We also observed the highest METTL5 expression level in KLE cells. Furthermore, knocking down METTL5 weakened the proliferation, reduced tumor volume and biomarkers, and increased apoptosis. Moreover, METTL5 knockdown induced the MSH2, MSH6 and PMS2 expression in MMR. METTL5 was negatively correlated with gene silencing, mRNA binding, olfactory receptor activity, antigen processing and presentation, cytosolic DNA sensing, olfactory transduction, and RIG-1-like and Toll-like receptor signaling pathways. METTL5 may regulate MMR protein levels in UCECs, thus enhancing UCEC proliferation, development, and prognosis.

RNA-binding protein with serine-rich domain 1 regulates microsatellite instability of uterine corpus endometrial adenocarcinoma

To determine the role of RNA-binding protein with serine-rich domain 1 (RNPS1) in uterine corpus endometrial carcinoma (UCEC), the role of RNPS1 knockdown in UCEC development in vitro and in vivo, and the relationship between RNPS1 and mismatch repair (MMR) in UCEC. We predicted the potential function of RNPS1 using bioinformatics systems. The expression of RNPS1 in tissues and cell lines was analyzed by western blotting and immunohistochemistry. The expression of RNPS1 in MMR was assessed using bioinformatics and western blotting. The proliferation and apoptosis of UCEC cells were assessed under RNPS1 knockdown conditions, and RNPS1 regulation in MMR was detected by suppressing Notch signaling. Associations between RNPS1 and gene mutations in UCEC and prognosis were analyzed. The RNPS1 level was higher in UCEC tumors than in normal tissues and tumors or RL952 cells. Prognostic outcomes were worse when UCEC showed abundant RNPS1 expression. Lentiviral RNPS1 knockdown weakened tumor cell proliferation and suppressed biomarker expression, reduced the tumor volume, promoted apoptosis in vitro and in vivo, and inhibited UCEC development. Increased MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) levels in MMR after RNPS1 knockdown were reversed by inhibiting Notch signaling. Furthermore, RNPS1 was associated with mutations in NAA11, C2orf57, NUPR1, and other genes involved in UCEC prognosis. RNPS1 may regulate the expression levels of MSH2 and MSH6 in MMR, enhancing the proliferation, development, and prognosis of UCEC through a Notch signaling pathway in UCEC. Our study offers a new method and strategy for delaying UCEC development through modulating MMR.